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Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis. Cell reports. Medicine Ohtsuki, S., Wang, C., Watanabe, R., Zhang, H., Akiyama, M., Bois, M. C., Maleszewski, J. J., Warrington, K. J., Berry, G. J., Goronzy, J. J., Weyand, C. M. 2023; 4 (4): 101012

Abstract

Loss of function of inhibitory immune checkpoints, unleashing pathogenic immune responses, is a potential risk factor for autoimmune disease. Here, we report that patients with the autoimmune vasculitis giant cell arteritis (GCA) have a defective CD155-CD96 immune checkpoint. Macrophages from patients with GCA retain the checkpoint ligand CD155 in the endoplasmic reticulum (ER) and fail to bring it to the cell surface. CD155low antigen-presenting cells induce expansion of CD4+CD96+ T cells, which become tissue invasive, accumulate in the blood vessel wall, and release the effector cytokine interleukin-9 (IL-9). In a humanized mouse model of GCA, recombinant human IL-9 causes vessel wall destruction, whereas anti-IL-9 antibodies efficiently suppress innate and adaptive immunity in the vasculitic lesions. Thus, defective surface translocation of CD155 creates antigen-presenting cells that deviate T cell differentiation toward Th9 lineage commitment and results in the expansion of vasculitogenic effector T cells.

View details for DOI 10.1016/j.xcrm.2023.101012

View details for PubMedID 37075705